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Iskalni niz: "avtor" (B. Lopez) .

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1.
Decontamination strategies and bloodstream infections with antibiotic-resistant microorganisms in ventilated patients : a randomized clinical trial
Bastiaan H. Wittekamp, Nienke L. Plantinga, Ben S. Cooper, Joaquin Lopez-Contreras, Pere Coll, Jordi Mancebo, Matt P. Wise, Matt P. G. Morgan, Pieter Depuydt, Jerina Boelens, Viktorija Tomič, Franc Šifrer, 2018

Povzetek: Importance: The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown. Objective: To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance. Design, setting, and participants: Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum [beta]-lactamase-producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017. Interventions: Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily. Main outcomes and measures: The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period. Results: A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, -0.6% to 1.1%), 0.6% (95% CI, -0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline. Conclusions and relevance: Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care.
Ključne besede: anti-infective agents -- therapeutic use, bacteremia -- prevention and control, chlorhexidine -- therapeutic use, cross infection -- prevention and control, disinfection -- methods, bacterial drug resistance, gastrointestinal tract -- microbiology, Gram-negative bacterial infections -- prevention and control, hospital mortality, intensive care units, mouthwashes -- therapeutic use, oropharynx -- microbiology, artificial respiration, multicenter study, randomized controlled trial
DiRROS - Objavljeno: 09.11.2020; Ogledov: 667; Prenosov: 184

2.
Detection of EGFR variants in plasma : a multilaboratory comparison of a real-time PCR EGFR mutation test in Europe
Cleo Keppens, John Palma, Partha Das, Sidney Scudder, Wei Wen, Nicola Normanno, Han J. J. M. van Krieken, Alessandra Sacco, Francesca Fenizia, David Gonzalez de Castro, Selma Hönigschnabl, Izidor Kern, Fernando Lopez-Rios, Maria D. Lozano, Antonio Marchetti, Philippe Halfon, Ed Schuuring, Ulrike Setinek, Boe Sorensen, Phillipe Taniere, Markus Tiemann, Hana Vosmikova, Elisabeth Dequeker, 2018

Povzetek: Molecular testing of EGFR is required to predict the response likelihood to targeted therapy in non-small cell lung cancer. Analysis of circulating tumor DNA in plasma may complement limitations of tumor tissue. This study evaluated the interlaboratory performance and reproducibility of a real-time PCR EGFR mutation test (cobas EGFR Mutation Test v2) to detect EGFR variants in plasma. Fourteen laboratories received two identical panels of 27 single-blinded plasma samples. Samples were wild type or spiked with plasmid DNA to contain seven common EGFR variants at six predefined concentrations from 50 to 5000 copies per milliliter. The circulating tumor DNA was extracted by a cell-free circulating DNA sample preparation kit (cobas cfDNA Sample Preparation Kit), followed by duplicate analysis with the real-time PCR EGFR mutation test (Roche Molecular Systems, Pleasanton, CA). Lowest sensitivities were obtained for the c.2156G>C p.(Gly719Ala) and c.2573T>G p.(Leu858Arg) variants for the lowest target copies. For all other variants, sensitivities varied between 96.3% and 100.0%. All specificities were 98.8% to 100.0%. Coefficients of variation indicated good intralaboratory and interlaboratory repeatability and reproducibility but increased for decreasing concentrations. Prediction models revealed a significant correlation for all variants between the predefined copy number and the observed semiquantitative index values, which reflect the samples' plasma mutation load. This study demonstrates an overall robust performance of the real-time PCR EGFR mutation test kit in plasma. Prediction models may be applied to estimate the plasma mutation load for diagnostic or research purposes.
Ključne besede: non-small cell lung cancer, plasma, EGFR, molecular testing
DiRROS - Objavljeno: 23.11.2020; Ogledov: 721; Prenosov: 101

3.
Emerging organic compounds in European groundwater
B. Lopez, A. Togola, M. E. van Vliet, L. Rosenqvist, Nina Mali, A. Kuczyńska, Anja Koroša, J. Grima-Olmedo, E. J. Crane, D. J. Lapworth, S. Y. Bunting

Povzetek: In Europe, emerging organic compounds (EOCs) in groundwater is a growing research area. Prioritisationfor monitoring EOCs in Europe was formalised in 2019 through the development of thefirst voluntarygroundwater watch list (GWWL). Despite this, groundwater occurrence data in the peer reviewedliterature for Europe has not been reviewed to date. Questions surrounding the effect, toxicity, move-ment in the subsurface and unsaturated zone make the process of regulating EOC use difficult. The aim inEurope is to develop a unified strategy for the classification, and prioritisation of EOCs to be monitored ingroundwater. This paper compiles evidence from the recent published studies from across Europe, since2012, when the last major literature global review of EOCs in groundwater took place. A total of 39studies were identified for review based on specific selection criteria (geography, publication date,sample size>10, inclusion of EOCs data). Data on specific compounds, and associated meta-data, arecompiled and reviewed. The two most frequently detected EOCs, carbamazepine and caffeine, occurredin groundwater at concentrations of up to 2.3 and 14.8mg/L, respectively.
Ključne besede: emerging organic chemicals, environmental exposure, groundwater contaminants, compounds of concern, groundwater hazards
DiRROS - Objavljeno: 13.01.2021; Ogledov: 832; Prenosov: 351
.pdf Celotno besedilo (1,90 MB)

4.
A meta-analysis of global fungal distribution reveals climate-driven patterns
Tomáš Větrovský, Petr Kohout, Martin Kopecky, Antonin Machac, Matěj Man, Barbara Doreen Bahnmann, Vendula Brabcová, Jinlyung Choi, Lenka Mészárosová, Zander Rainier Human, Clémentine Lepinay, Rubén López-Mondéjar, Tijana Martinović, 2019

Povzetek: The evolutionary and environmental factors that shape fungal biogeography are incompletely understood. Here, we assemble a large dataset consisting of previously generated mycobiome data linked to specific geographical locations across the world. We use this dataset to describe the distribution of fungal taxa and to look for correlations with different environmental factors such as climate, soil and vegetation variables. Our meta-study identifies climate as an important driver of different aspects of fungal biogeography, including the global distribution of common fungi as well as the composition and diversity of fungal communities. In our analysis, fungal diversity is concentrated at high latitudes, in contrast with the opposite pattern previously shown for plants and other organisms. Mycorrhizal fungi appear to have narrower climatic tolerances than pathogenic fungi. We speculate that climate change could affect ecosystem functioning because of the narrow climatic tolerances of key fungal taxa.
Ključne besede: fungi, global distribution, climate
DiRROS - Objavljeno: 03.01.2022; Ogledov: 170; Prenosov: 121
.pdf Celotno besedilo (1,59 MB)

5.
SERPING1 variants and C1-INH biological function : a close relationship with C1-INH-HAE
Christian Drouet, Alberto López Lera, Arije Ghannam, Margarita López-Trascasa, Sven Cichon, Denise Ponard, Faidra Parsopoulou, Hana Grombirikova, Tomas Freiberger, Matija Rijavec, Camila Lopes Veronez, João Bosco Pesquero, Anastasios E. Germenis, 2022

Povzetek: Hereditary angioedema with C1 Inhibitor deficiency (C1-INH-HAE) is caused by a constellation of variants of the SERPING1 gene (n = 809; 1,494 pedigrees), accounting for 86.8% of HAE families, showing a pronounced mutagenic liability of SERPING1 and pertaining to 5.6% de novo variants. C1-INH is the major control serpin of the kallikrein–kinin system (KKS). In addition, C1-INH controls complement C1 and plasminogen activation, both systems contributing to inflammation. Recognizing the failed control of C1s protease or KKS provides the diagnosis of C1-INH-HAE. SERPING1 variants usually behave in an autosomal-dominant character with an incomplete penetrance and a low prevalence. A great majority of variants (809/893; 90.5%) that were introduced into online database have been considered as pathogenic/likely pathogenic. Haploinsufficiency is a common feature in C1-INH-HAE where a dominant-negative variant product impacts the wild-type allele and renders it inactive. Small (36.2%) and large (8.3%) deletions/duplications are common, with exon 4 as the most affected one. Point substitutions with missense variants (32.2%) are of interest for the serpin structure–function relationship. Canonical splice sites can be affected by variants within introns and exons also (14.3%). For noncanonical sequences, exon skipping has been confirmed by splicing analyses of patients' blood-derived RNAs (n = 25). Exonic variants (n = 6) can affect exon splicing. Rare deep-intron variants (n = 6), putatively acting as pseudo-exon activating mutations, have been characterized as pathogenic. Some variants have been characterized as benign/likely benign/of uncertain significance (n = 74). This category includes some homozygous (n = 10) or compound heterozygous variants (n = 11). They are presenting with minor allele frequency (MAF) below 0.00002 (i.e., lower than C1-INH-HAE frequency), and may be quantitatively unable to cause haploinsufficiency. Rare benign variants could contribute as disease modifiers. Gonadal mosaicism in C1-INH-HAE is rare and must be distinguished from a de novo variant. Situations with paternal or maternal disomy have been recorded (n = 3). Genotypes must be interpreted with biological investigation fitting with C1-INH expression and typing. Any SERPING1 variant reminiscent of the dysfunctional phenotype of serpin with multimerization or latency should be identified as serpinopathy.
Ključne besede: Hereditary angioedemas -- genetics -- diagnosis, genetic variation, serpins, SERPING1 gene, C1-INH, C1-INH-HAE, C1 inhibitor, serpinopathy
DiRROS - Objavljeno: 06.04.2022; Ogledov: 97; Prenosov: 66
.pdf Celotno besedilo (2,51 MB)
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